P394: FRONTLINE COMBINATION OF OLVEREMBATINIB AND PDT-ALL-2016 PEDIATRIC INSPIRED PROTOCOL IN PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Kaibo Zhu, Ting Zhang, Zhixiang Wang, Qifa Liu, Hongsheng Zhou
Journal: HemaSphere (2023)

Background: Tyrosine kinase inhibitors (TKIs) combined standard chemotherapy have improved the long-term outcomes of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Previous studied showed that ponatinib, combined with Hyper-CVAD, result in modest rates of complete molecular response (CMR) of 75% in three months. Olverembatinib, a new potent third-generation TKI, shows well tolerated and significant-activity in patients with TKI-resistant CML but marginally analyzed in ALL. Aims: We hypothesized a strategy that combines the third-generation potent TKI, olverembatinib, and PDT-ALL-2016, (a pediatric inspired chemotherapy regimen in our institution) may increase the rate of CMR, reduce side effects in Chinese adults with Ph-positive ALL. Methods: The study included 16 adults (range 16-64) diagnosed as Ph-positive ALL. Patients have received 3 courses or less of chemotherapy according to PDT-ALL-2016 protocol, with olverembatinib orally administered at 40 mg once every other day. Complete Remission (CR) was defined as the normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count ≥1 * 10^9/L and platelet count ≥100 * 10^9/L, with complete resolution of all sites of extramedullary disease, and Complete Molecular Remission (CMR) was defined as absence of a detectable BCR-ABL1 transcript by polymerase-chain reaction (PCR) analysis at a sensitivity of 0.01%, and continuously monitor in day14, day30, day60 and day90 after receiving olverembatinib. Results: From September 4, 2021 to December 14, 2022, a total of 13 patients (13/16, others were excluded for too short treatment duration of olverembatinib) were enrolled in this study (Table). All 13 patients with a median follow-up of 8.967 months (range 6.422~11.511) enrolled achieved CR for an overall response rate of 100%. Median overall survival was not reached (Fig.A). CMR was achieved in 2/13 (15.4%), 5/13 (38.5%), 8/13 (61.3%), 11/13 (84.6%) in day14, day30, day60, day90, respectively (Fig.B). Third-generation TKI related adverse events were observed only in three patients, including skin hyperpigmentation (2/13), hypertension (1/13). A total of 6 patients (46.2%) received allo-HSCT after, and 1 died from pulmonary embolism after transplantation. Summary/Conclusion: The results of olverembatinib combined with PDT-ALL-2016 pediatric-inspired protocol continue to demonstrate excellent outcome results and acceptable safety data, indicating that this strategy maybe another standard of care approach in frontline Ph-positive ALL and further clinical trial is needed to conduct. (This work was supported by National Natural Science Foundation of China [81770170, 81970147, 82170163], Science and Technology Planning Project of Guangdong [2017A030313601], Clinical Trial Funding of SMU [2016A020215112], Clinical Trial Funding of Nanfang Hospital [LC2016ZD009/2019CR012])Keywords: Adult, BCR-ABL, Acute lymphoblastic leukemia